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Abstract:

A production process for a microneedle arrangement and a corresponding
microneedle arrangement as well as a use for it is disclosed. The process
has the following steps: forming an etching mask in grid form, with grid
bars with corresponding grid crossing regions and grid openings in
between on a substrate; carrying out an etching process to form the
microneedle arrangement on the substrate using the etching mask and
removing the etching mask. The etching mask in grid form has at least
some of the grid crossing regions flat reinforcing regions, which extend
beyond the grid bars.

Claims:

1. A production process for a microneedle arrangement, comprising:
forming an etching mask in grid form, with grid bars with corresponding
grid crossing regions and grid openings in between on a substrate;
carrying out an etching process to form the microneedle arrangement on
the substrate using the etching mask; and removing the etching mask,
wherein the etching mask in grid form has at least some of the grid
crossing regions flat reinforcing regions, which extend beyond the grid
bars.

2. The production process according to claim 1, wherein the etching mask
in grid form has at least first and second flat reinforcing regions of
different area extents and the etching process being carried out in such
a way that the microneedle arrangement has corresponding first and second
microneedles of different first and second heights, respectively.

3. The production process according to claim 1, wherein the substrate is
a silicon substrate and the etching mask is formed as an oxide mask.

4. The production process according to claim 1, wherein some of the grid
crossing regions possess no flat reinforcing regions.

5. The production process according to claim 4, wherein the grid crossing
regions that possess no flat reinforcing regions lie in an inner region
of the etching mask in grid form.

6. A microneedle arrangement comprising: a substrate; and a plurality of
microneedles formed on the substrate, said plurality of microneedles
possessing different heights with respect to each other.

7. The microneedle arrangement according to claim 6, wherein: said
plurality of microneedles including at least first and second
microneedles, and said first and second microneedles respectively possess
first and second heights that differ from each other.

8. The microneedle arrangement according to claim 7, wherein a difference
in height of the first and second heights lie in the range of 20% to 50%.

9. The microneedle arrangement according to claim 6, wherein: said
plurality of microneedles includes at least first, second, and third
microneedles, and said first, second, and third microneedles respectively
possess first, second, and third heights that differ from each other.

10. The microneedle arrangement according to claim 9, wherein the third
microneedles has a third height, which is the lowest height, and the
third microneedles being provided only in an inner region of the
microneedle arrangement.

11. The microneedle arrangement according to claim 6, wherein the
microneedle arrangement is configured for tattooing of a human body or an
animal body.

12. A microneedle arrangement including a plurality of microneedles which
are formed on a substrate and have different heights with respect to each
other, said microneedle arrangement being configured for tattooing a
human body or an animal body.

Description:

[0001] This application claims priority under 35 U.S.C. §119 to
German patent application no. DE 10 2010 030 864.1, filed Jul. 2, 2010 in
Germany, the disclosure of which is incorporated herein by reference in
its entirety.

BACKGROUND

[0002] The present disclosure relates to a production process for a
microneedle arrangement and to a corresponding microneedle arrangement as
well as to a use for it.

[0003] Although it can be applied to any micromechanical components, the
present disclosure and the background on which it is based are explained
with regard to micromechanical components in silicon technology.

[0004] Microneedle arrangements, which for example comprise microneedles
of porous silicon, are used in the area of "transdermal drug delivery" as
a supplement to medicament plasters, as a carrier of a vaccine and also
for obtaining body fluid (known as "transdermal fluid") for the diagnosis
and analysis of body parameters (for example glucose, lactate, . . . ).

[0005] Medicament plasters (transdermal patches) for small molecules (for
example nicotine) are widely known. To extend the application area for
such transdermal applications of active substances, use is made of
so-called chemical enhancers or various physical methods (ultrasound,
heat pulses), which help to overcome the protective covering that is the
skin.

[0006] A further method for this is mechanical perforation of the outer
layers of skin (stratum corneum) by fine porous microneedles, combined
with the administration of an active substance, preferably via an active
substance plaster in which the microneedles may already be integrated, or
via a dosing device, which makes a specific release (bolus, pause,
increase, . . . ) of active substances possible.

[0007] DE 10 2006 028 781 A1 discloses a process for producing porous
microneedles arranged in an array on a silicon substrate for the
transdermal administration of medicaments. The process comprises forming
on the front side of a semiconductor substrate a microneedle arrangement
with a plurality of microneedles, which rise up from a supporting region
of the semiconductor substrate, as well as partially porosifying the
semiconductor substrate to form porous microneedles, the porosifying
being performed from the front side of the semiconductor substrate and a
porous reservoir being formed.

[0008] DE 10 2006 028 914 A1 discloses a process for producing
microneedles from porous material, a coating of silicon being applied
over a microneedle arrangement while the tips of the needles remain
uncovered, after which a process of porosifying the microneedles is
carried out.

[0009] DE 10 2006 040 642 A1 discloses a microneedle arrangement for
placement in the skin for the purpose of transdermal application of
pharmaceuticals.

[0010] FIGS. 8a,b are schematic representations for the explanation of a
production process given by way of example for a microneedle arrangement,
to be precise FIG. 8a is a plan view of an etching grid and FIG. 8b is a
cross-sectional view of the etching grid and of the microneedle
arrangement resulting from it along the line A-A' from FIG. 8a.

[0011] In FIG. 8, reference sign 10 denotes an etching mask, which is
applied to a silicon substrate 1. The etching mask 10 is, for example, an
oxide mask, which is produced by a suitable photolithographic process on
the silicon substrate 1 after a full-area oxidation or oxide deposition.

[0012] The etching mask 10 has the form of a regular square etching grid
with horizontal grid bars 100 and vertical grid bars 110 orthogonal
thereto. Reference sign 10a denotes a respective grid crossing region
between the grid bars 100 and 110. Reference sign 10b denotes a
respective grid opening, through which an etching medium can pass to the
silicon substrate 1 during the etching process, in order to porosify it
and thus form the microneedles.

[0013] The structuring of a microneedle arrangement 20 with a plurality of
microneedles 200 arranged in the form of a matrix corresponding to the
etching grid 10 takes place by an anisotropic etching process known per
se (for example DRIE) and an isotropic plasma etching process. The
anisotropic etching process and the isotropic etching process may either
be carried out once, one after the other, that is to say first
anisotropic and then isotropic, or else in an alternating manner, for
example anisotropic-isotropic-anisotropic-isotropic- . . . and so on.

[0014] After the etching, the microneedles 200 remain under the grid
crossing regions 10a. In the case of the etching mask 10 that is used
according to FIGS. 8a,b, a supporting region la of the semiconductor
substrate 1 is also left behind at the foot of the microneedles 200.

[0015] After the etching, the etching mask 10 spans the microneedle
arrangement 20 and is suspended over the substrate 1 in a peripheral
region not represented. The exposure of the microneedle arrangement 20 by
removing the etching mask takes place by an oxide etching step.
Porosifying can then be performed, if desired, in a further known etching
step.

[0016] A functional aspect of a microneedle arrangement is that the
needles are intended to pierce the skin as well as possible, i.e. they
should be as pointed as possible, but also must not be too close, since
otherwise an undesired "Fakir effect" occurs, that is to say hindered
penetration of the needles into the skin. On the other hand, a desired
effect, for example a great transfer of active substance, often requires
as many needles as possible and correspondingly many piercings of the
skin. If, however, this is at the expense of a large area, the costs
increase rapidly, since they are in linear proportion to the wafer area
that is required for a selected process.

SUMMARY

[0017] The production process according to the disclosure for a
microneedle arrangement and the corresponding microneedle arrangement as
well as the use have the advantage that the grid crossing regions of the
etching mask are reinforced in terms of their surface area in comparison
with the grid bars, in order in this way to produce thicker and more
stable microneedles in the etching process.

[0018] If, for example, microneedles of different heights are placed next
to one another within a microneedle arrangement, the longer microneedles
can penetrate the skin first, and the somewhat shorter ones then follow
into the already penetrated skin, which makes the piercing process more
reliable, more effective and more stable. Patterns which can for example
be used for tattooing can also be generated.

[0019] One effect of using the etching masks according to the disclosure
is that inhomogeneities on the substrate surface after the etching
processes can be corrected, so that a uniform microneedle array is
obtained over the wafer, which is accompanied by an increased yield.

[0020] The features set forth in the disclosure make a specifically
adaptable height pattern of the microneedles possible within a
microneedle arrangement, which can be adapted according to the
application, and whereby not only the piercing characteristics but also
the stability of the needles can be adapted to requirements.

[0021] The features presented in the dependent claims relate to
advantageous developments and improvements of the relevant subject matter
of the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Exemplary embodiments of the disclosure are explained in more
detail in the description which follows and are represented in the
drawing, in which:

[0023] FIGS. 1a,b show schematic representations for the explanation of a
first embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 1a shows a plan view of
an etching grid and FIG. 1b shows a cross-sectional view of the etching
grid and of the microneedle arrangement resulting from it along the line
A-A' from FIG. 1a;

[0024] FIGS. 2a,b show schematic representations for the explanation of a
second embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 2a shows a plan view of
an etching grid and FIG. 2b shows a cross-sectional view of the etching
grid and of the microneedle arrangement resulting from it along the line
A-A' from FIG. 2a;

[0025] FIGS. 3a,b show schematic representations for the explanation of a
third embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 3a shows a plan view of
an etching grid and FIG. 3b shows a cross-sectional view of the etching
grid and of the microneedle arrangement resulting from it along the line
A-A' from FIG. 3a;

[0026] FIGS. 4a,b show schematic representations for the explanation of a
fourth embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 4a shows a plan view of
an etching grid and FIG. 4b shows a cross-sectional view of the etching
grid and of the microneedle arrangement resulting from it along the line
A-A' from FIG. 4a;

[0027] FIGS. 5a,b show schematic representations for the explanation of a
fifth embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 5a shows a plan view of
an etching grid and FIG. 5b shows a cross-sectional view of the etching
grid and of the microneedle arrangement resulting from it along the line
A-A' from FIG. 5a;

[0028]FIG. 6 shows a plan view of an etching grid for the explanation of
a sixth embodiment of the production process according to the disclosure
for a microneedle arrangement;

[0029]FIG. 7 shows a plan view of an etching grid for the explanation of
a seventh embodiment of the production process according to the
disclosure for a microneedle arrangement; and

[0030] FIGS. 8a,b show schematic representations for the explanation of a
production process for a microneedle arrangement given by way of example,
to be precise FIG. 8a shows a plan view of an etching grid and FIG. 8b
shows a cross-sectional view of the etching grid and of the microneedle
arrangement resulting from it along the line A-A' from FIG. 8a.

DETAILED DESCRIPTION

[0031] In the figures, the same reference signs denote elements that are
the same or functionally the same.

[0032] FIGS. 1a,b are schematic representations for the explanation of a
first embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 1a is a plan view of an
etching grid and FIG. 1b is a cross-sectional view of the etching grid
and of the microneedle arrangement resulting from it along the line A-A'
from FIG. 1a.

[0033] In the case of the first embodiment, reference sign 10' denotes an
etching mask, which like the etching mask 10 according to FIGS. 8a,b
comprises a regular orthogonal grid of horizontal grid bars 100' and
vertical grid bars 110'. The grid crossing regions are denoted by
reference sign 10'a and the grid openings are denoted by reference sign
10'b.

[0034] By contrast with the etching mask 10 described above, the etching
mask 10' has at the grid crossing regions 10'a square reinforcing regions
115', which have a greater cross section than the grid bars 100', 110'
and which extend beyond the grid bars 100', 110' into the grid openings
10'b.

[0035] If the anisotropic/isotropic etching process already described in
connection with FIG. 8 is applied to a silicon substrate 1 which is
covered by the etching mask 10' of oxide, the form of microneedles
represented in FIG. 1b is obtained, comprising thicker, more stable
microneedles 200' than the microneedles 200 in FIG. 8b. In particular,
the supporting region 1a according to FIG. 8b has almost completely
disappeared in the case of the microneedle arrangement 20' according to
FIG. 1b.

[0036] FIGS. 2a,b are schematic representations for the explanation of a
second embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 2a is a plan view of an
etching grid and FIG. 2b is a cross-sectional view of the etching grid
and of the microneedle arrangement resulting from it along the line A-A'
from FIG. 2a.

[0037] In the case of the second embodiment according to FIG. 2, reference
sign 10'' denotes an etching mask of oxide, which likewise has horizontal
grid bars 100'' and vertical grid bars 110'', which are arranged in an
orthogonal form. In the case of the etching mask 10'', the grid crossing
regions are denoted by 10''a and the grid openings are denoted by 10''b.

[0038] As a difference from the first embodiment described above, in the
case of the second embodiment the square reinforcing regions 115''a and
115''b at the grid crossing regions 10''a vary with regard to their
surface area. For instance, in the case of the present example, the first
reinforcing regions 115''a have a larger surface area than the second
reinforcing regions 115''b.

[0039] If the anisotropic/isotropic etching process described above is
applied in the case of such an etching mask 10'', higher, thicker
microneedles 200''a and narrower, lower microneedles 200''b are created,
as represented in FIG. 2b. The higher, thicker microneedles 200''a form
under the larger reinforcing regions 115''a, and the narrower, lower
microneedles 200''b form under the smaller reinforcing regions 115''b.

[0040] After the anisotropic etching process, the narrower and thicker
microneedles still have in fact the same height, but during the isotropic
etching process the narrower microneedles are etched more quickly and
lose height in comparison with the thicker microneedles, so that the
microneedle arrangement 20'' shown in FIG. 2b is obtained.

[0041] A typical size for the thicker, higher microneedles 200''a is a
height h1=180 μm, a typical order of size for the narrower, lower
microneedles 200''b is a height h2=120 μm. Tests have shown that
extremely efficient piercing characteristics can be achieved if the
difference in height between the microneedles 200''a and 200''b is in the
range of 20-50%.

[0042] FIGS. 3a,b are schematic representations for the explanation of a
third embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 3a is a plan view of an
etching grid and FIG. 3b is a cross-sectional view of the etching grid
and of the microneedle arrangement resulting from it along the line A-A'
from FIG. 3a.

[0043] In the case of the third embodiment, the etching mask 10'''
likewise has horizontal grid bars 100''' and vertical grid bars 110',
which are arranged in the orthogonal grid form already described.

[0044] In the case of the etching mask 10''', at the grid crossing regions
10'''a first reinforcing regions 115'''a with a larger area or second
reinforcing regions 115'''b with a smaller area are provided and at
certain grid crossing regions 10'''a no reinforcing regions at all are
provided. The latter grid crossing regions lie in the inner region IB of
the etching mask 10''' or of the resulting microneedle arrangement 20'''
with the grid openings 10'b.

[0045] As represented in FIG. 3b, three different types of microneedle
200'''a, 200'b and 200'c can be produced in the microneedle arrangement
20''' by means of the etching mask 10''' in the etching process already
described above. The first microneedles 200'''a are thicker needles with
a greater height h1 of typically 180 μm, the second microneedles
200'''b are narrower, lower microneedles with a height h2 of typically
120 μm, and the third microneedles 200'''c are very narrow, very low
microneedles with a height h3 of typically 90 μm.

[0046] As shown in FIGS. 3a,b, the three microneedles 200'''c are not
arranged in the outer region AB of the microneedle arrangement 200''',
but in the inner region IB thereof. In other words, they are shielded
from the outer region AB by the first microneedles 200'''a, so that, for
example in the case of porous microneedles of silicon, the risk of
breakage due to canting can be reduced or avoided.

[0047] FIGS. 4a,b are schematic representations for the explanation of a
fourth embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 4a is a plan view of an
etching grid and FIG. 4b is a cross-sectional view of the etching grid
and of the microneedle arrangement resulting from it along the line A-A'
from FIG. 4a.

[0048] In the case of the fourth embodiment, the etching mask 11'''
likewise has horizontal grid bars 100''' and vertical grid bars 110',
which are arranged in the orthogonal grid form already described.

[0049] In the case of the etching mask 11''', at the grid crossing regions
10'a first reinforcing regions 115'''a with a larger area or second
reinforcing regions 115'b with a smaller area are provided and at certain
grid crossing regions 10'''a no reinforcing regions at all are provided.
The latter grid crossing regions lie in the outer region AB' of the
etching mask 11' or of the resulting microneedle arrangement 21''' with
the grid openings 10'b.

[0050] As represented in FIG. 4b, three different types of microneedle
200'''a, 200'b and 200'c can be produced in the microneedle arrangement
21''' by means of the etching mask 11''' in the etching process already
described above. The first microneedles 200'''a are thicker needles with
a greater height h1 of typically 180 μm, the second microneedles
200'''b are narrower, lower microneedles with a height h2 of typically
120 μm, and the third microneedles 200'''c are very narrow, very low
microneedles with a height h3 of typically 90 μm.

[0051] As shown in FIGS. 4a,b, the height of the microneedles 200'a,
200'''b, 200'''c increases in stages from the outer region AB' to the
inner region IB'.

[0052] FIGS. 5a,b are schematic representations for the explanation of a
fifth embodiment of the production process according to the disclosure
for a microneedle arrangement, to be precise FIG. 5a is a plan view of an
etching grid and FIG. 5b is a cross-sectional view of the etching grid
and of the microneedle arrangement resulting from it along the line A-A'
from FIG. 5a.

[0053] In the case of the fifth embodiment, the etching mask 12' likewise
has horizontal grid bars 100''' and vertical grid bars 110', which are
arranged in the orthogonal grid form already described.

[0054] In the case of the etching mask 12''', at the grid crossing regions
10'a first reinforcing regions 115'''a with a larger area or second
reinforcing regions 115'b with a smaller area are provided and at certain
grid crossing regions 10'''a no reinforcing regions at all are provided.
The latter grid crossing regions lie in the inner region IB'' of the
etching mask 12' or of the resulting microneedle arrangement 22'' with
the grid openings 10'b.

[0055] As represented in FIG. 5b, three different types of microneedle
200'''a, 200'b and 200'c can be produced in the microneedle arrangement
20''' by means of the etching mask 12''' in the etching process already
described above. The first microneedles 200'''a are thicker needles with
a greater height h1 of typically 180 nm, the second microneedles 200'''b
are narrower, lower microneedles with a height h2 of typically 120 nm,
and the third microneedles 200'''c are very narrow, very low microneedles
with a height h3 of typically 90 nm.

[0056] As shown in FIGS. 5a,b, the height of the microneedles 200'a,
200'''b, 200'''c decreases in stages from the outer region AB'' to the
inner region IB''.

[0057]FIG. 6 is a plan view of an etching grid for the explanation of a
sixth embodiment of the production process according to the disclosure
for a microneedle arrangement.

[0058] In the case of the sixth embodiment, the etching mask 13'''
likewise has horizontal grid bars 100''' and vertical grid bars 110',
which are arranged in the orthogonal grid form already described.

[0059] In the case of the etching mask 13''', at the grid crossing regions
10'a first reinforcing regions 115'''a are provided and at certain grid
crossing regions 10'a no reinforcing regions at all are provided. The
first reinforcing regions 115'''a are arranged in such a way that the
etching mask assumes an "X" pattern. This "X" pattern is transferred
during the etching to the corresponding microneedle arrangement, which
then can be used for example in conjunction with a tattooing fluid for
the tattooing of a human or animal body.

[0060]FIG. 7 is a plan view of an etching grid for the explanation of a
seventh embodiment of the production process according to the disclosure
for a microneedle arrangement.

[0061] In the case of the seventh embodiment, the etching mask 14'''
likewise has horizontal grid bars 100' and vertical grid bars 110''',
which are arranged in the orthogonal grid form already described.

[0062] In the case of the etching mask 13''', at the grid crossing regions
10'a first reinforcing regions 115'''a are provided and at certain grid
crossing regions 10'a no reinforcing regions at all are provided. The
first reinforcing regions 115'''a are arranged in such a way that the
etching mask assumes a "" pattern. This "" pattern is transferred during
the etching to the corresponding microneedle arrangement, which then can
likewise be used for example for tattooing.

[0063] Although the present disclosure has been described above on the
basis of preferred exemplary embodiments, it is not restricted to these
but can be modified in various ways.

[0064] Although in the case of the embodiments described above certain
materials have been described, for example silicon as the substrate and
oxide for the etching mask, the present disclosure is not restricted to
these but can be applied to any materials that have corresponding etching
characteristics or a corresponding etching selectivity.

[0065] The grid form of the etching mask is also not restricted to the
orthogonal, square form shown but can in principle be applied to any
forms of grid. The reinforcing regions at the grid crossing regions do
not have to be square but may assume any geometry, for example also a
round geometry or a rhomboidal geometry, etc.

[0066] Furthermore, the present disclosure is not restricted to porous
microneedles of silicon but can in principle be applied to any
microneedles that can be produced in an etching process using an etching
mask.